Reference:
GGP08258
Abstract:
Rett syndrome (RTT) is the major cause of mental retardation in female children. This pathology is caused by mutations affecting the MECP2 gene located on chromosome X, that in normal conditions regulates the expression of numerous genes. Recently, it has been found that BDNF is one of the target genes of MeCP2 and it is expressed at lower levels in animal models of RTT. BDNF is a neurotrophic factor fundamental for neuronal survival, maturation and plasticity during development. In particular, BDNF is involved in neuronal shaping of dendritic arborisation that is altered in RTT. Indeed, RTT is characterised by neurons with reduced dimensions and complexity of dendritic branching, causing the reduction of cerebral volume and synaptic connections. Two recent studies have demonstrated that in RTT animal models it is possible to reverse the disease course through genetic manipulations capable to increase BDNF expression. Considered that gene therapy has to deal with several technical problems we decided to follow a pharmacological approach to treat Rett syndrome. This strategy is based on the evidence that in RTT animal models there are detectable alterations of BDNF mRNA levels that can be increased with compounds normally used in the treatment of depression. In this project, we propose to systematically evaluate the compounds able to induce BDNF protein synthesis in cellular and animal models of Rett syndrome. Remarkably, clinical applications of experimental evidence would be rapid, due to the fact that the investigated compounds are already present in pharmaceutical market. Scientific publications
PROJECT DETAILS
beginning: 2008.
end: 2011.
Country of research: Italy
Counry of funding source: Italy
Funding organization: Telethon
Financing: PRIVATE FUNDERS – 99 700 €